In the 1980s, Peterle started working at the Institute for Urban planning of the Socialist Republic of Slovenia. In the mid-1980s, he was involved in several projects of trans-regional cooperation within the Alpe-Adria regional cooperation network.

Peterle served as deputy prime minister and foreign minister from January 1993 until October 1994. Tensions were deep in the coalition, however, and Peterle resigned from his posts in 1994 when Drnovšek nominated Jožef Školč, a member of his own Liberal Democratic Party, to be speaker of Parliament, against the wishes of Peterle who believed that a Christian Democrat should be the speaker. The Christian Democrats did remain in the coalition, which was often divided over specific policy issues. In 1996, Peterle called for the dismissal of foreign minister Zoran Thaler because of his belief that Thaler did not do enough to help Slovenia's relations with Italy.

Between 1996 and 2000, the Christian Democrats remained in opposition, and Peterle's leadership was frequently challenged by different fractions within the party. He nevertheless managed to remain the chairman of the Party until 2000, when the Christian Democrats merged with the Slovenian People's Party, which had until then supported Janez Drnovšek's third term as Prime Minister. As a consequence, Drnovšek's government fell in 2000, and Peterle became foreign minister again in the short-lived centre-right government of Andrej Bajuk from June 2000 to November 2000.

In addition to his committee assignments, Peterle has been chairing the parliament's delegation to the EU-former Yugoslav Republic of Macedonia Joint Parliamentary Committee since 2014. He previously served on the delegations for relations with the countries of Southeast Asia and the Association of Southeast Asian Nations (2004-2009), to the EU-Russia Parliamentary Cooperation Committee (2009-2014), to the EU-Croatia Joint Parliamentary Committee (2009-2013) and for relations with Japan (2013-2014).

In November 2006, Peterle announced that he would be running for President of Slovenia in the 2007 presidential election. Backed by most of the centre-right government,[3] he was considered the front-runner before the first round of the election, but ultimately lost in a landslide to Danilo Türk in the second round.